Profilin 1 is essential for retention and metabolism of mouse hematopoietic stem cells in bone marrow

Junke Zheng, Zhigang Lu, Fatih Kocabas, Ralph T. Böttcher, Mercedes Costell, Xunlei Kang, Xiaoye Liu, Ralph J DeBerardinis, Qianming Wang, Guo Qiang Chen, Hesham A Sadek, Chengcheng Zhang

Research output: Contribution to journalArticle

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Abstract

How stem cells interact with the microenvironment to regulate their cell fates and metabolism is largely unknown. Here we demonstrated that the deletion of the cytoskeleton-modulating protein profilin 1 (pfn1) in hematopoietic stem cell (HSCs) led to bone marrow failure, loss of quiescence, and mobilization and apoptosis of HSCs in vivo. A switch from glycolysis to mitochondrial respiration with increased reactive oxygen species (ROS) level was also observed in HSCs on pfn1 deletion. Importantly, treatment of pfn1-deficient mice with the antioxidant N-acetyl-L-cysteine reversed the ROS level and loss of quiescence of HSCs, suggesting that the metabolism is mechanistically linked to the cell cycle quiescence of stem cells. The actin-binding and proline-binding activities of pfn1 are required for its function in HSCs. Our study provided evidence that pfn1 at least partially acts through the axis of pfn1/Gα13/EGR1 to regulate stem cell retention and metabolism in the bone marrow.

Original languageEnglish (US)
Pages (from-to)992-1001
Number of pages10
JournalBlood
Volume123
Issue number7
DOIs
StatePublished - Feb 13 2014

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Profilins
Hematopoietic Stem Cells
Stem cells
Metabolism
Bone
Bone Marrow
Stem Cells
Reactive Oxygen Species
Hematopoietic Stem Cell Mobilization
Acetylcysteine
Glycolysis
Cytoskeleton
Proline
Actins
Cell Cycle
Respiration
Antioxidants
Apoptosis
Cells
Switches

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Profilin 1 is essential for retention and metabolism of mouse hematopoietic stem cells in bone marrow. / Zheng, Junke; Lu, Zhigang; Kocabas, Fatih; Böttcher, Ralph T.; Costell, Mercedes; Kang, Xunlei; Liu, Xiaoye; DeBerardinis, Ralph J; Wang, Qianming; Chen, Guo Qiang; Sadek, Hesham A; Zhang, Chengcheng.

In: Blood, Vol. 123, No. 7, 13.02.2014, p. 992-1001.

Research output: Contribution to journalArticle

Zheng, J, Lu, Z, Kocabas, F, Böttcher, RT, Costell, M, Kang, X, Liu, X, DeBerardinis, RJ, Wang, Q, Chen, GQ, Sadek, HA & Zhang, C 2014, 'Profilin 1 is essential for retention and metabolism of mouse hematopoietic stem cells in bone marrow', Blood, vol. 123, no. 7, pp. 992-1001. https://doi.org/10.1182/blood-2013-04-498469
Zheng, Junke ; Lu, Zhigang ; Kocabas, Fatih ; Böttcher, Ralph T. ; Costell, Mercedes ; Kang, Xunlei ; Liu, Xiaoye ; DeBerardinis, Ralph J ; Wang, Qianming ; Chen, Guo Qiang ; Sadek, Hesham A ; Zhang, Chengcheng. / Profilin 1 is essential for retention and metabolism of mouse hematopoietic stem cells in bone marrow. In: Blood. 2014 ; Vol. 123, No. 7. pp. 992-1001.
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